PMID- 10201973 OWN - NLM STAT- MEDLINE DCOM- 19990506 LR - 20131121 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 162 IP - 8 DP - 1999 Apr 15 TI - Cutting edge: effects of an allergy-associated mutation in the human IL-4R alpha (Q576R) on human IL-4-induced signal transduction. PG - 4385-9 AB - A mutation in the human (hu) IL-4R alpha, Q576R, has been linked with allergy in humans. Increased sensitivity of patients cells with this mutation to IL-4 suggest that a Q576R change enhances IL-4 signaling. To directly test this hypothesis, we analyzed the ability of huIL-4R alpha cDNA bearing the Q576R and Y575F mutations to signal tyrosine phosphorylation, DNA-binding activity, proliferation, protection from apoptosis, and CD23 induction in response to huIL-4 in murine cells. Responses generated by the Q576R and Y575F mutants were similar to those of the wild-type receptor, using various concentrations of huIL-4 and times of stimulation. These results indicate that neither the Q576R nor the Y575F mutations have a significant direct effect on IL-4 signal transduction, and that hypersensitive induction of CD23 in cells derived from human allergy patients may be due to different and/or additional alterations in the IL-4 signaling pathway. FAU - Wang, H Y AU - Wang HY AD - Department of Immunology, Jerome Holland Laboratories, American Red Cross, Rockville, MD 20855, USA. FAU - Shelburne, C P AU - Shelburne CP FAU - Zamorano, J AU - Zamorano J FAU - Kelly, A E AU - Kelly AE FAU - Ryan, J J AU - Ryan JJ FAU - Keegan, A D AU - Keegan AD LA - eng GR - AI38985/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (DNA-Binding Proteins) RN - 0 (IRS1 protein, human) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Irs1 protein, mouse) RN - 0 (Phosphoproteins) RN - 0 (Receptors, IgE) RN - 0 (Receptors, Interleukin-4) RN - 0 (STAT6 Transcription Factor) RN - 0 (STAT6 protein, human) RN - 0 (Stat6 protein, mouse) RN - 0 (Trans-Activators) RN - 0RH81L854J (Glutamine) RN - 42HK56048U (Tyrosine) RN - 94ZLA3W45F (Arginine) RN - EC 2.7.10.1 (Receptor, Insulin) SB - IM MH - Amino Acid Substitution/genetics/immunology MH - Animals MH - Apoptosis/genetics/immunology MH - Arginine/genetics MH - Cell Line MH - DNA-Binding Proteins/biosynthesis MH - Glutamine/genetics MH - Humans MH - Hypersensitivity/*genetics/immunology MH - Insulin Receptor Substrate Proteins MH - Lymphocyte Activation/genetics MH - Mice MH - Mutagenesis, Site-Directed/*immunology MH - Phosphoproteins/metabolism MH - Phosphorylation MH - Receptor, Insulin/metabolism MH - Receptors, IgE/biosynthesis MH - Receptors, Interleukin-4/*genetics/physiology MH - STAT6 Transcription Factor MH - Signal Transduction/genetics/*immunology MH - Trans-Activators/metabolism MH - Tyrosine/genetics/metabolism EDAT- 1999/04/14 00:00 MHDA- 1999/04/14 00:01 CRDT- 1999/04/14 00:00 PHST- 1999/04/14 00:00 [pubmed] PHST- 1999/04/14 00:01 [medline] PHST- 1999/04/14 00:00 [entrez] PST - ppublish SO - J Immunol. 1999 Apr 15;162(8):4385-9.